阅读说明：本技术 一种含双酰胺结构的两性离子单体及其制备方法 (Zwitterionic monomer containing bisamide structure and preparation method thereof ) 是由 刘文广 陈薪羽 杨建海 于 2019-09-18 设计创作，主要内容包括：本发明提供一种含双酰胺结构的两性离子单体及其制备方法,首先以N,N’-亚甲基双丙烯酰胺(MBAA)和二甲胺为原料,通过迈克尔加成反应获得一端叔胺化的MBAA产物即第一步产物；再以第一步产物和丙烯酸为原料,在三乙胺的作用下,最终得到一种含双酰胺结构的两性离子单体。本发明单体制备方法简单,反应条件温和,可实现大批量制备,通过聚合反应易于制备两性离子基材料,其具有良好的抗生物污染能力,在船体抗污和生物医疗器械上都具有广泛应用。(The invention provides a zwitterionic monomer containing a bisamide structure and a preparation method thereof, which comprises the following steps of firstly, taking N, N' -Methylene Bisacrylamide (MBAA) and dimethylamine as raw materials, and obtaining an MBAA product with one end being subjected to tertiary amination through Michael addition reaction, namely a first-step product; and finally obtaining the zwitterion monomer containing the bisamide structure by taking the product of the first step and acrylic acid as raw materials under the action of triethylamine. The monomer of the invention has simple preparation method and mild reaction condition, can realize mass preparation, is easy to prepare the zwitterion-based material through polymerization reaction, has good biological pollution resistance and has wide application in ship body pollution resistance and biomedical instruments.)

1. A zwitterionic monomer containing a bisamide structure is characterized in that: the zwitterionic monomer containing the bisamide structure consists of quaternary ammonium salt and carboxylate, and the chemical formula is as follows:

the method comprises the following steps:

step 1, dissolving N, N ' -Methylene Bisacrylamide (MBAA) and dimethylamine in an organic solvent, reacting for 12-60h at 10-50 ℃, and purifying to obtain an N, N ' -Methylene Bisacrylamide (MBAA) monomer with a tertiary aminated double bond at one end, namely a first-step product, wherein the molar ratio of the N, N ' -Methylene Bisacrylamide (MBAA) to the dimethylamine is (1-5) to (1-2);

and 2, dissolving the first-step product prepared in the step 1 and acrylic acid in an organic solvent, reacting at 5-40 ℃ for 12-78h, adding triethylamine into the mixed solution, reacting at 5-40 ℃ for 12-30h, and purifying to obtain the zwitterion monomer containing the bisamide structure, wherein the molar ratio of the first-step product to the acrylic acid is (1-2): 1-8, and the molar ratio of the first-step product to the triethylamine is (1-2): 1-10).

2. The zwitterionic monomer of claim 1, wherein: in the step 1, the molar ratio of N, N' -Methylene Bisacrylamide (MBAA) to dimethylamine is (1-4):1, the reaction temperature is 10-40 ℃, the reaction time is 12-48h, and the organic solvent adopts methanol.

3. The zwitterionic monomer of claim 1, wherein: in the step 2, the molar ratio of the product of the first step to acrylic acid is 1 (1-6), the reaction temperature is 5-30 ℃, the reaction time is 12-72h, and the organic solvent adopts acetone.

4. The zwitterionic monomer of claim 1, wherein: in the step 2, the molar ratio of the product of the first step to triethylamine is 1 (1-8), the reaction temperature is 5-30 ℃, and the reaction time is 12-24 h.

5. A preparation method of a zwitterionic monomer containing a bisamide structure is characterized by comprising the following steps: the method comprises the following steps:

step 1, dissolving N, N ' -Methylene Bisacrylamide (MBAA) and dimethylamine in an organic solvent, reacting for 12-60h at 10-50 ℃, and purifying to obtain an N, N ' -Methylene Bisacrylamide (MBAA) monomer with a tertiary aminated double bond at one end, namely a first-step product, wherein the molar ratio of the N, N ' -Methylene Bisacrylamide (MBAA) to the dimethylamine is (1-5) to (1-2);

and 2, dissolving the first-step product prepared in the step 1 and acrylic acid in an organic solvent, reacting at 5-40 ℃ for 12-78h, adding triethylamine into the mixed solution, reacting at 5-40 ℃ for 12-30h, and purifying to obtain the zwitterion monomer containing the bisamide structure, wherein the molar ratio of the first-step product to the acrylic acid is (1-2): 1-8, and the molar ratio of the first-step product to the triethylamine is (1-2): 1-10).

6. The method for preparing the zwitterionic monomer with the bisamide structure according to claim 5, wherein: in the step 1, the molar ratio of N, N' -Methylene Bisacrylamide (MBAA) to dimethylamine is (1-4):1, the reaction temperature is 10-40 ℃, the reaction time is 12-48h, and the organic solvent adopts methanol.

7. The method for preparing the zwitterionic monomer with the bisamide structure according to claim 5, wherein: in the step 2, the molar ratio of the product of the first step to the acrylic acid is 1 (1-6), the reaction temperature is 5-30 ℃, and the reaction time is 12-72 h.

8. The method for preparing the zwitterionic monomer with the bisamide structure according to claim 5, wherein: in the step 2, the molar ratio of the product of the first step to triethylamine is 1 (1-8), the reaction temperature is 5-30 ℃, and the reaction time is 12-24 h.

9. The method for preparing the zwitterionic monomer with the bisamide structure according to claim 5, wherein: in step 2, acetone is used as the organic solvent.

Technical Field

The invention relates to the technical field of synthesis of zwitterionic compounds, in particular to a zwitterionic monomer containing a bisamide structure and a preparation method thereof.

Background

Zwitterionic materials such as Carboxybetaine (CB) and Sulfobetaine (SB) materials, which have high dipole moments and high charge groups but remain electrically neutral overall, have different applications due to their unique molecular structures. Currently, zwitterionic materials are used as a biocompatible material that resists non-specific protein adsorption in serum, increases and does not inactivate enzymes in urea, and does not induce an immune response during blood circulation. Studies have shown that zwitterionic materials have ultra-low contamination in single protein solutions and undiluted serum plasma due to their ultra-strong hydration. Compared with Sulphobetaine (SB), the Carboxyl Betaine (CB) material has stronger antifouling capacity, can be functionalized and is convenient for protein fixation; can maintain the multifunctionality of stem cells, can not induce the nonspecific differentiation of the stem cells, and can be used for biosensing and targeted drug delivery.

The zwitterion material can also be used as an antifouling coating and also applied to the fields of biosensors, implantable medical devices, marine ships and the like. The marine organism fouling causes the increase of the navigation resistance of the ship body, the reduction of the navigation speed, and the blockage and damage of pipelines; biological fouling of implanted equipment can cause adverse reactions such as thrombus, blood coagulation, immunity, infection and the like to a human body. The zwitterionic material has a good protective effect for this.

Disclosure of Invention

The invention overcomes the defects in the prior art, and provides the zwitterionic monomer containing the bisamide structure and the preparation method thereof.

The purpose of the invention is realized by the following technical scheme.

A zwitterion monomer containing a bisamide structure, wherein the zwitterion consists of a quaternary ammonium salt and carboxylate and has the following chemical formula:

a preparation method of a zwitterionic monomer containing a bisamide structure comprises the following steps:

step 1, dissolving N, N ' -Methylene Bisacrylamide (MBAA) and dimethylamine in an organic solvent, reacting for 12-60h at 10-50 ℃, and purifying to obtain an N, N ' -Methylene Bisacrylamide (MBAA) monomer with a tertiary aminated double bond at one end, namely a first-step product, wherein the molar ratio of the N, N ' -Methylene Bisacrylamide (MBAA) to the dimethylamine is (1-5) to (1-2);

and 2, dissolving the first-step product prepared in the step 1 and acrylic acid in an organic solvent, reacting at 5-40 ℃ for 12-78h, adding triethylamine into the mixed solution, reacting at 5-40 ℃ for 12-30h, and purifying to obtain the zwitterion monomer containing the bisamide structure, wherein the molar ratio of the first-step product to the acrylic acid is (1-2): 1-8, and the molar ratio of the first-step product to the triethylamine is (1-2): 1-10).

In the step 1, the molar ratio of N, N' -Methylene Bisacrylamide (MBAA) to dimethylamine is (1-4):1, the reaction temperature is 10-40 ℃, and the reaction time is 12-48 h.

In step 1, methanol is used as the organic solvent.

In the step 2, the molar ratio of the product of the first step to the acrylic acid is 1 (1-6), the reaction temperature is 5-30 ℃, and the reaction time is 12-72 h.

In the step 2, the molar ratio of the product of the first step to triethylamine is 1 (1-8), the reaction temperature is 5-30 ℃, and the reaction time is 12-24 h.

In step 2, acetone is used as the organic solvent.

The invention has the beneficial effects that: the invention adopts N, N' -Methylene Bisacrylamide (MBAA), dimethylamine and acrylic acid as raw materials to prepare the zwitterionic monomer containing the bisamide structure. The monomer has unsaturated carbon-carbon double bonds, a bisamide structure and a zwitterion structure, so that the monomer has excellent anti-pollution capability. The synthesis method of the invention has few byproducts, and the prepared zwitterionic monomer product has high purity and hydrophilicity; the synthetic method is simple to operate and mild in reaction condition. The prepared zwitterionic monomer containing the bisamide structure can be used for polymerization reaction and physical crosslinking network due to the double bond and the bisamide structure, and can be applied to biocompatible materials, antifouling coatings and biosensors; the synthesis raw materials adopted in the synthesis process are low in cost, and industrial production is facilitated.

Drawings

FIG. 1 is a schematic diagram of the preparation of a zwitterionic monomer containing a bisamide structure according to the invention;

FIG. 2 is a nuclear magnetic spectrum of the zwitterionic monomer containing a bisamide structure prepared in example 1 of the present invention.

Detailed Description

The technical solution of the present invention is further illustrated by the following specific examples.

Example 1

3.08g N, N' -Methylenebisacrylamide (MBAA), 5.00mL of dimethylamine were dissolved in 80mL of methanol and reacted at 20 ℃ with stirring for 48 hours, and then the mixture after the reaction was completed was rotary-evaporated. And adding 20mL of acetone and 3mL of acrylic acid into the rotary evaporation product, stirring and reacting for 48h at 20 ℃, adding 20mL of triethylamine, stirring for 24h, centrifuging, washing with acetone, dimethyl sulfoxide (DMSO) and diethyl ether for multiple times, centrifuging, and drying in vacuum to obtain white zwitterionic monomer powder containing a bisamide structure.

As shown in fig. 2, the structure of the zwitterionic monomer containing the bisamide structure obtained in example 1 is characterized by nmr hydrogen spectroscopy: 1H-NMR (400MHz, D)₂O): δ 6.26(2H), 5.83(1H), 4.69(2H), 3.67(2H), 3.60(2H), 3.11(6H), 2.86(2H), 2.76 (3H). Wherein 6.26 and 5.83 are characteristic peaks of the double bond of the monomer; 4.69 is the characteristic peak for the methylene group between the two amide bonds; the absorption peaks with splits at 3.67, 3.60, 2.86 and 2.76 are characteristic peaks of four methylene groups in the monomer; the peak at 3.11 is the characteristic peak of the methyl group on the quaternary ammonium salt. There are two solvent peaks in the nuclear magnetic map due to the use of methanol and dimethyl sulfoxide (DMSO) for monomer synthesis and purification.

Example 2

13g N, N' -Methylene Bisacrylamide (MBAA) and 35mL of dimethylamine are dissolved in 250mL of methanol, the mixture is stirred and reacted for 12 hours at 10 ℃, and then the mixture after the reaction is finished is evaporated in a rotary manner. Adding 200mL of acetone and 19mL of acrylic acid into the rotary evaporation product, stirring and reacting for 48h at 25 ℃, adding 60mL of triethylamine, stirring for 12h, centrifuging, washing with acetone, dimethyl sulfoxide (DMSO) and diethyl ether for multiple times, centrifuging, and drying in vacuum to obtain white zwitterionic monomer powder containing a bisamide structure.

Example 3

8g N, N' -Methylene Bisacrylamide (MBAA) and 50mL of dimethylamine are dissolved in 150mL of methanol, the mixture is stirred and reacted for 12 hours at 40 ℃, and then the mixture after the reaction is finished is evaporated in a rotary manner. Adding 200mL of acetone and 15mL of acrylic acid into the rotary evaporation product, stirring and reacting for 72h at 30 ℃, adding 55mL of triethylamine, stirring for 24h, centrifuging, washing with acetone, dimethyl sulfoxide (DMSO) and diethyl ether for multiple times, centrifuging, and drying in vacuum to obtain white zwitterionic monomer powder containing a bisamide structure.

Example 4

N, N' -Methylene Bisacrylamide (MBAA) and dimethylamine in a molar ratio of 5:2 were dissolved in 150mL of methanol and reacted at 50 ℃ with stirring for 12 hours, and then the mixture after the reaction was completed was rotary-evaporated. Adding 200mL of acetone and acrylic acid into the rotary evaporation product, wherein the molar ratio of the first-step product to the acrylic acid is 1:8, stirring and reacting for 12h at 40 ℃, adding triethylamine, stirring for 12h, washing the product with the triethylamine for multiple times by acetone, dimethyl sulfoxide (DMSO) and diethyl ether after centrifugation, centrifuging, and drying in vacuum to obtain white zwitterion monomer powder containing a bisamide structure.

Example 5

N, N' -Methylene Bisacrylamide (MBAA) and dimethylamine in a molar ratio of 1:2 were dissolved in 150mL of methanol and reacted at 10 ℃ with stirring for 60 hours, and then the mixture after the reaction was completed was rotary-evaporated. Adding 200mL of acetone and acrylic acid into the rotary evaporation product, wherein the molar ratio of the first-step product to the acrylic acid is 2:7, stirring and reacting at 5 ℃ for 78h, adding triethylamine, stirring for 30h, washing with acetone, dimethyl sulfoxide (DMSO) and diethyl ether for multiple times after centrifugation, centrifuging, and drying in vacuum to obtain white zwitterion monomer powder containing a bisamide structure.

The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.